El-Mabhouh Amal, Mercer John R
Faculty of Pharmacy and Pharmaceutical Sciences, 3118 Dentistry Pharmacy Center, University of Alberta, Edmonton Alta, Canada T6G-2N8.
Appl Radiat Isot. 2005 Apr;62(4):541-9. doi: 10.1016/j.apradiso.2004.10.004.
Two new bisphosphonates have been examined for their ability to bind 188Re and deliver it selectively to bone. The bisphosphonates are prototype compounds with potential to deliver rhenium radionuclides and a second therapy modality to bone metastases. A conjugate between diethylenetriaminepentaacetic acid and bisphosphonate (DTPA/BP) and a conjugate between 5-fluorouracil and bisphosphonate (5-FU/BP) were prepared and labeled at high radiochemical purity with 188Re and biodistribution studies were carried out in normal Balb/C mice. The compounds showed rapid blood clearance and elimination from soft tissues with substantial retention of activity in the bone comparable to 188Re-hydroxyethylidine diphosphonate used as a control. At 8 h bone activity was 3.51% of injected dose for 188Re-DTPA/BP and 6.38% of injected dose for 188Re-5-FU/BP representing 69.6% and 80.6% of total body radioactivity, respectively. The two compounds show the potential for combination therapy of painful bone metastases.
已对两种新型双膦酸盐结合¹⁸⁸Re并将其选择性递送至骨骼的能力进行了研究。这些双膦酸盐是具有将铼放射性核素和第二种治疗方式递送至骨转移灶潜力的原型化合物。制备了二乙烯三胺五乙酸与双膦酸盐的缀合物（DTPA/BP）以及5-氟尿嘧啶与双膦酸盐的缀合物（5-FU/BP），并以高放射化学纯度用¹⁸⁸Re进行标记，然后在正常Balb/C小鼠中进行生物分布研究。这些化合物显示出快速的血液清除和从软组织的消除，骨骼中的活性大量保留，与用作对照的¹⁸⁸Re-羟基亚乙基二膦酸盐相当。在8小时时，¹⁸⁸Re-DTPA/BP的骨活性为注射剂量的3.51%，¹⁸⁸Re-5-FU/BP的骨活性为注射剂量的6.38%，分别占全身放射性的69.6%和80.6%。这两种化合物显示出对疼痛性骨转移进行联合治疗的潜力。
